Modulation of the immune response by complement may occur through the interaction of C3- and C4-derived ligands with complement receptors on lymphocytes and macrophages. Two structurally related complement receptors, CRl and CR2, that bind C3b/C4b and C3dg, respectively, are present on B lymphocytes. Analysis of their role in proliferative and antigen-presenting reactions of B cells is the aim of this project. Three functions of CR2 on B cells that are potentially growth promoting have been identified. First, crosslinking CR2 and membrane IgM on B cells caused a synergistic increase in free intracellular calcium concentration relative to that observed with crosslinking IgM alone; CR2 alone had no affect. CRl also was without affect alone and did not synergize with membrane IgM. Studies are proposed to determine the basis for this interaction between CR2 and membrane IgM. Second, preincubation of B cells with C3dg for 24 hr caused the cells to enter S phase more rapidly following stimulation with anti-IgM. The role of CR2 in this priming reaction will be defined. Third, addition of C3dg to serum-free culture medium prolonged by four-fold the half-life of B cells. The requirement for crosslinking CR2 in this reaction will be examined. The antigen-presenting functions of CRl and CR2 on B cells will be analyzed by preparing fluorescein (FL)- conjugated oligomers of C3b, C3bi, and C3dg. EBV-transformed B cells that have been pulsed with the FL-C3/C4 fragments or with FL- albumin as a control will be assessed for their capacity to present FL to autologous, FL-specific T cell lines. The T cells that have been activated in this manner will be examined for their capacity to activate reciprocally the antigen-presenting B cell. Demonstration of these reactions would provide a model that describes a role for complement in antigen-specific activation of T cells, and in T cell-dependent, antigen-non-specific, polyclonal B cell activation.